ABSTRACT
CRISPR-Cas loci of bacteria and archaea provide adaptive immunity against viruses that infect these organisms (phages). CRISPR loci consist in an array of short repetitive sequences (~ 30 bp) separated by equally short “spacer” sequences of viral origin that are acquired upon viral infection. Spacer sequences are transcribed into small antisense RNAs that guide CRISPR-associated (Cas) nucleases to the phage genome for its destruction. Temperate phages usually carry beneficial genes for the host (even essential in certain conditions) that are incorporated into the bacterial genome after the integration of the viral DNA, or lysogeny. Therefore these phages can be considered commensals and their destruction by CRISPR immunity can be detrimental for the cell fitness. Here we investigated whether this immune system can tolerate commensal viruses. We found that, at least in staphylococci, Cas-mediated cleavage requires transcription of the target DNA. As most of the viral genes are silenced upon lysogeny, this requirement facilitates the tolerance of the lysogen. Tolerance, however, is contingent to the “good behavior” of the phage. When the lysogen initiates a lytic cycle, of lethal consequences for the host, its genome is transcribed and thus becomes a target for Cas nucleases. Therefore the staphylococcal CRISPR-Cas immune system possesses a tolerance mechanism that allows the cell to “domesticate” its viruses: maintaining them when they provide beneficial traits, but destroy them if they become harmful.